Olivomycin A is a member of the aureolic acid group of antitumor antibiotics. Three members of this group (olivomycin A, chromomycin A3 and mithramycin) have been used clinically for the treatment of various tumors, but toxicity limits their usefulness. Various studies establish that the oligosaccharides play key roles in the recognition and binding of the aureolic acids to DNA. We propose to complete a highly stereoselective synthesis of olivomycin A, thereby defining a strategy that may be useful for the synthesis of analogues with unnatural oligosaccharides and improved therapeutic indices. Syntheses of the aglycone, olivin, and the AB disaccharide have been completed, and a highly stereoselective method for the synthesis of aryl Beta-2-deoxyglycosides has been developed for use in coupling of the AB disaccharide to the aglycone. The last remaining problem is the establishment of an efficient method for the synthesis of the three 2-deoxy-Beta-glycosidic linkages that occur in the CDE trisaccharide. While CD disaccharides 41 and 44 were synthesized in the preceding grant period, the selectivity for the Beta-glycosides was less than desired owing to the unanticipated nucleophile dependent, configurational instability of the 2alpha-phenylselenyl glycosyl acetates 37 and 38 that were used as the glycosyl donors. Efforts in the coming grant year will focus on the 2alpha-phenylthio glycoside donors 102-106 since preliminary results indicate that the 2alpha-PhS substituted glycosides show no tendency to epimerize via reversible episulfonium ion intermediates. The prospects that this synthesis will be completed in the next grant period are very good. Studies of the exo-anomeric effect as a stereocontrol element in asymmetric and acyclic diastereoselective synthesis will be continued. In the preceding grant period we discovered that the chiral (Z)-gamma- alkoxyallylstannane 64 containing a mannosyl auxiliary exhibits excellent diastereofacial control in BF3 catalyzed reactions with chiral aldehydes. The generality of this process for the synthesis of syn diols 124 will be fully explored. Improved auxiliaries (e.g., 137) will develop if required to maximize stereoselectivity. This strategy will be extended to the development of a chiral (E)-gamma-mannosylallylchromium reagent 142 for the enantioselective synthesis of anti diols 125. This "alpha- hydroxyallylation" methodology should prove very useful in the synthesis of carbohydrates and other polyhydroxylated natural products. Two targets of immediate interest are castanospermine (150) and swainsonine (151). Synthetic methodology previously developed in our laboratory will be applied in highly stereoselective total syntheses of mycalamides A and B, a group of potent antiviral and antitumor agents.